Circulating levels of atherogenesis-associated adipocytokines and apoptotic markers are differentially influenced by hormone therapy, tibolone and raloxifene in healthy postmenopausal women.

OBJECTIVE: Estrogen agonist compounds may exert cardioprotective activity by modulating adipocytokine concentration and apoptosis. The objective of this study was to evaluate the effects of hormone therapy, tibolone and raloxifene on the serum adipocytokines resistin and adiponectin as well as on circulating markers of receptor-mediated apoptosis. Design Randomized, open-label, intervention study in the Menopause Clinic of a University Hospital. METHODS: One hundred healthy postmenopausal women were randomized to the following groups: conjugated equine estrogens 0.625 mg (CEE) (n = 16); 17 beta-estradiol 1 mg plus norethisterone acetate 0.5 mg (E(2)/NETA) (n = 15); tibolone 2.5 mg (n = 18); raloxifene HCl 60 mg (n = 20); and no treatment (n = 19). Eighty-eight women completed the 3-month study period. Main outcome measures were levels of serum adiponectin, resistin, soluble Fas and Fas ligand. RESULTS: Levels of serum adiponectin decreased significantly in the tibolone group (baseline: 10 556.7 +/- 4213.5 ng/ml; 3 months: 7856.3 +/- 3450.7 ng/ml; p = 0.0001) and increased in the CEE group (baseline: 9268.1 +/- 5158 ng/ml; 3 months: 11 302.6 +/- 4980.9 ng/ml; p = 0.01). Serum resistin values increased only in the tibolone group (baseline: 2.81 +/- 0.89 ng/ml; 3 months: 3.55 +/- 1.31 ng/ml; p = 0.04), while the level of Fas ligand decreased significantly in the E2/NETA (baseline: 70.4 +/- 21.9 pg/ml; 3 months: 62.1 +/- 18.6 pg/ml; p = 0.02) and tibolone group (baseline: 68.2 +/- 25.7 pg/ml; 3 months: 59.2 +/- 21.7 pg/ml; p = 0.01). CONCLUSIONS: Of the regimens investigated, only unopposed estrogens may exert an atheroprotective effect through the increase of adiponectin and a resultant favorable lipid and anti-inflammatory profile.

Effect of hormone replacement therapy, tibolone and raloxifene on serum lipids, apolipoprotein A1, apolipoprotein B and lipoprotein(a) in Greek postmenopausal women.

The aim of this study was to assess the effect of estrogen, two regimens of continuous combined hormone replacement therapy (HRT), tibolone and raloxffene on serum lipid, apolipoprotein A1 and B and lipoprotein(a) levels in Greek postmenopausal women. A total of 350 postmenopausal women were studied in a prospective open design. Women were assigned to one of the following regimens depending on the presence of risk factors for osteoporosis, dimacteric symptoms and an intact uterus: conjugated equine estrogen 0.625 mg (CEE, n = 34), continuous combined CEE 0.625 mg plus medroxyprogesterone acetate (MPA) 5 mg, (n = 80), continuous combined 17beta-estradiol 2 mg plus norethisterone acetate (NETA) 1 mg (n = 58), tibolone 2.5 mg (n = 83) and raloxifene HCl 60 mg (n = 50). Forty-five postmenopausal women with no indications for HRT served as controls. Total cholesterol (TC), low-density lipoprotein (LDL) cholestrol and high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and lipoprotein(a) (Lp(a)) levels were assessed in each subject at baseline, and at 6 and 12 months of therapy. All therapy regimens lowered TC levels compared to baseline (4.2-8.0% decrease). This effect was more prominent in the subgoup of women with high baseline TC levels (9.1-20.4% decrease). LDL cholesterol decreased significantly in CEE, CEE/MPA and raloxifene groups (-11.2%, -11.9% and -11.0%, respectively). Hypercholesterolemic women exhibited a steeper decrease in LDL cholesterol (10.6-27.8% in all therapy groups). TG levels increased significantly in the CEE and CEE/MPA groups (23.7% and 21.8%, respectively), while estradiol/NETA had no effect on TG levels. Tibolone decreased TG levels markedly, by 20.6%, while raloxifene had no TG-lowering effect. HDL cholesterol and ApoA1 were increased by CEE and CEE/MPA (HDL cholesterol, 7.4% and 11.8%, respectively; ApoA1, 17.8% and 7.9%, respectively) and decreased by tibolone (HDL cholesterol, -13.6%; and ApoA1, -9.9%). All therapy regimens except raloxifene lowered Lp(a) levels, with tibolone having the more pronounced effect (-13.2 to -29.0%). In conclusion, each therapy regimen had a diferent effect on lipid-lipoprotein levels, exerting favorable and unfavorable modifications. Hypercholesterolemic women seemed to benefit more from the cholesterol-lowering effect of estrogen replacement therapy/HRT. The choice for a particular regimen should be based on individual needs, indications and lipid-lipoprotein profile.